The compound (1α,2β,4β,5α,7β)-7-[(hydroxydi-2-thienylacetyl)oxy]-9,9-dimethyl-3-oxa-9-azoniatricyclo[3.3.1.02,4]nonane-bromide, is known from European Patent Application EP 418 716 A1 and has the following chemical structure:

The compound has valuable pharmacological properties and is known by the name tiotropium bromide (BA679). Tiotropium bromide is a highly effective anticholinergic and can therefore provide therapeutic benefit in the treatment of asthma or COPD (chronic obstructive pulmonary disease).
Tiotropium bromide is preferably administered by inhalation. Suitable inhalable powders packed into appropriate capsules and administered by suitable powder inhalers may be used. Alternatively, it may be administered by the use of suitable inhalable aerosols. These also include powdered inhalable aerosols which contain, for example, HFA134a, HFA227 or mixtures thereof as propellant gas.
In view of the administration of tiotropium bromide by inhalation it is necessary to provide the active substance in a finely divided (or micronised) form. Preferably, the active substance has an average particles size of 0.5 to 10 μm, preferably from 1 to 6 μm, most preferably from 1.5 to 5 μm.
The above particles sizes are generally achieved by grinding (so-called micronisation) of the active substance. As breakdown of the pharmaceutically active substance must be prevented as far as possible as a side-effect of the micronisation, in spite of the hard conditions required for the process, high stability of the active substance during the grinding process is absolutely essential. It should be borne in mind that in some cases, during the grinding process, changes may occur to the solid properties of the active substance, which may influence the pharmacological properties of the formulation which is to be inhaled.
Methods of micronising pharmaceutically active substances are known as such in the prior art. The aim of the present invention is to provide a method which makes micronised tiotropium bromide available in a form which satisfies the stringent requirements imposed on an active substance intended for inhalation and thus takes account of the specific properties of tiotropium bromide.